The treatment of chronic pain has proven notoriously difficult. Patients experiencing causalgia, sympathetic dystrophy, phantom-limb syndrome, denervation or herpetic pain are generally resistant to opiates in the sense that opiates will obtund the pain but will not significantly change the experience of the patient's pain.
Peptides have been used in attempts to treat such syndromes with little, if any, success. For example, substance P has been implicated in the pathogenesis of chronic pain such as neurogenic edema and causes significant pain of a burning and aching nature when injected subcutaneously. Somatostatin does exert modulatory effects on substance P (as well as a wide variety of other growth factors) but is very short-lived.
Psoriatic arthritis has been reported as possibly treatable with somatostatin by slow intravenous infusion; however, the side effects appear to be such that use of this drug should be limited to psoriatic patients with polyarthritis or with severe cutaneous involvement. Matucci-Cernic et al., Intl. J. Dermatology, 27, pp. 56-58 (1988).
Recently, a longer acting analog of somatostatin has been synthesized with eight amino acids. This peptide (also termed "octreotide") and its analogs exhibit GH (growth hormone) secretion-inhibiting activity as indicated, for example, by depression of serum GH levels in rats and described by U.S. Pat. No. 4,395,403, issued Jul. 26, 1983, inventors Bauer et al. This patent describes use of these peptides in treating gastrointestinal disorders or excess GH-secretion.
British Patent No. 2,193,891, published Feb. 24, 1988, inventors Azria et al. discloses nasal octreotide compositions for the purposes of treating disorders with an etiology associated with excess GH-secretion or gastrointestinal disorders. The nasal compositions include the octreotide and a non-ionic absorption promoter, such as various surfactants, for promoting absorption of the nasal mucosa.
Webber et al., Surgery, 102, pp. 974-981 (1987) describes studies with octreotide combined with two penetrant enhancers--dimethylsulfoxide or N-decylmethylsulfoxide. Particular amounts were topically applied to samples of skin from human cadavers and hairless mice for the potential use in treating endocrine disorders and insulin-dependent diabetes mellitus. The test data indicated very slow transdermal passage of the octreotide when combined with dimethylsulfoxide and compared with the octreotide in N-decylmethylsulfoxide. However, the authors concluded that the octreotide permeates both human and mouse skin when applied topically with N-decylmethylsulfoxide.